ASO-mediated depletion of toxic mutant proteins is likely to be most critical in ALS, and should be joined with a gamut of neuroprotective accessory therapies such as neurotrophic factors (Henriques et al., 2010), SMN upregulation (e.g., via nusinersen or AVXS-101) (Kariya et al., 2012; Turner et al., 2014), and preservation of NMJ innervation (Miyoshi et al., 2017), in order to determine the most efficacious drug combinations. Here, SMN1 is linked to amyotrophic lateral sclerosis.